Endosomal-lysosomal system (ELS)

The endosomal-lysosomal system (ELS) is a complex, interconnected network of membrane-bound organelles responsible for the uptake, sorting, and degradation of extracellular and intracellular macromolecules. Endosomes act as sorting hubs that direct cargo toward recycling or degradation, while lysosomes serve as the primary digestive center, housing a variety of acid hydrolases that function optimally at a low pH (NIH, 2023). Beyond degradation, the ELS is a critical signaling platform that regulates nutrient sensing, autophagy, and immune responses, such as antigen presentation (PubMed, 2021). Dysregulation of this system is a primary cause of lysosomal storage diseases and a major contributor to neurodegenerative pathologies, including Alzheimer's and Parkinson's diseases, where the failure of the ELS leads to toxic protein aggregation (StatPearls, 2023). In drug development, the ELS is targeted through strategies such as enzyme replacement, substrate reduction, and the modulation of organellar pH using lysosomotropic agents (PubChem, 2024). Furthermore, the acidic environment and specific protease activity within lysosomes are frequently leveraged for the site-specific activation of prodrugs and antibody-drug conjugates (Nature Reviews Drug Discovery, 2022).

Other names

LysosomeEndosomeLysosomes/endosomesEndocytic pathwayVacuolar system

Inhibition of endosomal acidification, enzyme replacement, substrate reduction, pharmacological chaperoning, and lysosomal membrane permeabilization (Nature Reviews Drug Discovery, 2022; PubMed, 2021).